Assessment of the prevalence of vCJD through testing tonsils and appendices for abnormal prion protein

The objective of this study was to determine the age group or groups which will provide the most information on the potential size of the vCJD epidemic in Great Britain via the sampling of tonsil and appendix material to detect the presence of abnormal prion protein (PrP(Sc)). A subsidiary aim was to determine the degree to which such an anonymous age-stratified testing programme will reduce current uncertainties in the size of the epidemic in future years. A cohort- and time-stratified model was used to generate epidemic scenarios consistent with the observed vCJD case incidence. These scenarios, together with data on the age distribution of tonsillectomies and appendectomies, were used to evaluate the optimal age group and calendar time for undertaking testing and to calculate the range of epidemic sizes consistent with different outcomes. The analyses suggested that the optimal five-year age group to test is 25-29 years, although a random sample of appendix tissue from all age groups is nearly as informative. A random sample of tonsil tissue from all age groups is less informative, but the information content is improved if sampling is restricted to tissues removed from those over ten years of age. Based on the assumption that the test is able to detect infection in the last 75% of the incubation period, zero detected infections in an initial random sample of 1000 tissues would suggest that the epidemic will be less than 870,000 cases. If infections are detected, then the model prediction suggests that both relatively small epidemics (800+ cases if one is detected or 8300+ if two are detected) and larger epidemics (21,000+ cases if three or more are detected) are possible. It was concluded that testing will be most informative if undertaken using appendix tissues or tonsil tissues removed from those over ten years of age. Large epidemics can only be excluded if a small number of infections are detected and the test is able to detect infection early in the incubation period.     

Evaluation of the efficacy of split-product trivalent A(H1N1), A(H3N2), and B influenza vaccines: protective efficacy

A total of 1,995 primary school children (1,464 vaccinees and 531 non-vaccinees) were studied to evaluate the protective efficacy of Tween-ether split trivalent A(H1N1), A(H3N2), and B influenza vaccines by comparison of the incidence of confirmed infection in two groups during 1980 to 1984. During the study period, epidemics caused by antigenically different influenza viruses, that is A(H1N1) epidemics in 1981 and 1984, a B epidemic in 1982 and an A(H3N2) epidemic in 1983, were experienced, and at the same time strains changed by antigenic drift were frequently isolated. In these epidemics, 61% to 87% of the children reported respiratory illnesses and 18% to 48% of the illnesses were influenza confirmed by seroconversion. Throughout these four epidemics, the incidence of confirmed infection among the vaccinees (7.8% to 33.8%) was 6.5% to 34.8% lower than that among the nonvaccinees (35.4% to 51.6%), demonstrating that the vaccine was effective (X2 = 76.34, P less than 0.001). However, this effectiveness was not seen in an epidemic in one of the entrant schools in 1984, possibly caused by a strain with intense antigenic drift. On the basis of data on incidence of various symptoms, duration of fever and the number of days of absence from class, it was considered that clinical symptoms in the vaccinees were milder than those in the nonvaccinees. When the titers of hemagglutination-inhibiting (HAI) antibody against the vaccine strains were measured, the protective level of HAI antibody giving less than or equal to 50% incidence of infection was 1:64, but it increased to 1:256 in the 1984 epidemic, reflecting the high rate of isolates with intense antigenic drift.     

Characterization of the foci of meningococcal infection in closed groups of males

A total of 257 foci of meningococcal infection in groups of servicemen were selectively examined in 1982-2002. From these groups 353 patients with generalized forms of the disease underwent hospitalization. Most of the foci had a single infection, the proportion of foci with 10-40 patients was 82.6%. The meningococcal infection rate among humans in the foci was 25-37%, group A meningococci playing the leading role. In the structure of meningococcal infection generalized forms of infection constituted 16%, localized forms constituted 25% and inapparent forms (carriers)--59%. The formation of the morbidity structure was influenced by the type of the focus (with a single or multiple infection) and the character of morbidity for many years (during epidemic or at the period between epidemics). No absolute dependence of the level of meningococcal carrier state in the groups of servicemen on the appearance of the generalized forms of meningococcal infection was noted. Thus, both during epidemic and at the period between epidemics the population of meningococci, heterogeneous in its serological structure and differing in its clinical and epidemiological importance, constantly circulated with the leading role played by group A meningococci.     

Impacts of trichomonosis epidemics on Greenfinch Chloris chloris and Chaffinch Fringilla coelebs populations in Finland

Population consequences of parasites in wild birds are rarely documented. One exception is the decline of British finch populations due to an epidemic caused by the protozoan parasite Trichomonas gallinae. Finch trichomonosis has recently spread from the UK to northern Europe, but its consequences for local finch populations have not been studied. We assessed the extent to which the trichomonosis epidemic affected the Finnish population sizes of European Greenfinch Chloris chloris, Common Chaffinch Fringilla coelebs and a control species, Great Tit Parus major, and the body condition of Greenfinches. The disease was first documented in Finland in 2008 and epidemics were observed mainly in southwestern Finland. Greenfinches showed a significant decline of 47% in breeding numbers and 65% in wintering numbers in southern Finland during 2006–2010. Breeding Chaffinch numbers showed a slight decline (4%) during the same study period that was significant only in central Finland. Great Tit did not show a significant change in breeding numbers. During the initial disease epidemic the body condition of all demographic groups of Greenfinches decreased equally, which suggests that the disease was not selective in respect of age or sex. There were no encounters of Finnish‐ringed Greenfinches or Chaffinches in the UK, which could indicate that the parasite has not necessarily been transferred directly from the UK, but perhaps by migrants from Sweden and Germany.     

Incidence of meningococcal infection in the RSFSR]

The authors present characteristics of meningococcus infection epidemic process in case of sporadic cases and under epidemic conditions (1965--1976). A scheme of epidemiological analysis suggested by the authors permitted to differentiate and to record the incidence of various clinical forms of meningococcus infection, to present data on the age, seasonal characteristics, focality, etc. Comparison of intensive morbidity indices for 10 years, both at the individual administration territories and in the Republic as a whole demonstrated morbidity level of 1.5--2.0 to be one of prognostic signs of the beginning epidemic. The main features differentiating the sporadic and epidemic morbidity periods were revealed. The presence of group diseases, a greater percentage of children among those who fell ill, and marked signs of seasonality and territorial difference characterized the period of rise caused by meningococcus of serological group A.     

The epidemic spread of the influenza A and B viruses in the USSR in 1985-1986

The data on the spread of influenza A and B in the autumn and winter of 1985-1986 are given. Three epidemics caused by all presently circulating viruses, B, A (H3N2) and A (H1N1), were registered in the USSR. Of these, the greatest one was the epidemic of influenza B; morbidity rate among the adult population during this epidemic was at the level with the morbidity rate characteristic of the epidemics registered at the period of 1962-1972, and morbidity rate among children, especially school children, was even higher.     

Asian Influenza in 1963 in Two General Practices in Cambridge,England

A clinical, epidemiological and virological investigation was conducted on patients in two general practices in Cambridge, England, during an influenza epidemic between February and April 1963. The epidemiological pattern differed from that of the 1957-58 Asian influenza epidemic in that the overall incidence was considerably lower (3.2%) and that the highest attack rates were not in school children but in pre-school children (71.5 per 1000 persons).Virological investigation confirmed the diagnosis of Influenza A2 infection in 56 of 63 patients (89%). Isolations were made in 29 of 51 specimens tested. Serological studies revealed that the complement fixation test was more reliable than hemagglutination - inhibition or neutralization tests. Clinical features resembled those reported in previous epidemics, cough, headache and limb pains being prominent features.     

Epidemiological analysis of acute respiratory diseases (ARD) of viral etiology in the Czech Socialist Republic (CSR] and German Democratic Republic (GDR) over the period 1979 to 1984

An analysis is made of the ARD reported in CSR and the GDR over the period July 1st, 1979 to June 30th, 1984. During that time, there were 27,810,000 cases reported in CSR in the framework of ARD epidemiological surveillance, representing 2.67 cases per one inhabitant, whereas in the GDR, the total number of reported ARD was 28,900,000 yielding 1.73 cases per person. However, the GDR reported higher morbidity per one child of preschool age. The authors believe that the differences in the reported incidence of ARD between the two countries are due to differences in the reporting systems and medical officers' activity during an epidemic and in the interim period. Approximately one third of ARD reported annually in the two countries falls to the period of influenza epidemics. The authors also analyze the etiology of the influenza epidemics which affected the two countries in 1980, 1981, 1982, 1983 and 1984. In most seasons, the causative agents and morbidity excesses were different in the two countries. The drift variant B/USSR/100/83, which caused a major epidemy in CSR in 1984, has not to date been implicated in the DGR in the etiology of ARD. The cyclic epidemic due to Mycoplasma pneumoniae occurred in the GDR already in 1979-80, while CSR experienced it a year later. There was a temporal and territorial correlation between the course of A(H1N1) influenza epidemic in the two countries in 1984.     

The effect of the pine woolly aphid (Pineus pini) on survival,growth and natural selection in Scots pine (Pinus sylvestris) in Iceland

1. Scots pine Pinus sylvestris was originally introduced to Iceland in the beginning of the 20th Century. Extensive plantings started in the late 1940s and, in total, 2–3 million Scots pine seedlings were planted, mainly originating from two counties in northern Norway. Part of this plant material was imported as seedlings.
2. Pine woolly aphid Pineus pini was introduced to Iceland before 1940, most likely on imported seedlings in 1937.
3. High mortality of Scots pine, concurrent with high infestation of the pine woolly aphid, was observed in Iceland during the late 1950s and 1960s and planting was discontinued.
4. Provenance trials with Scots pine were established in Iceland in 2004–2006. They consisted of 15 provenances from Norway, four from Finland, four from Scotland, one from Russia, one from the Austrian Alps and three first generation Scots pine provenances from Iceland, collected from survivors of the epidemic in the 1950s and 1960s. In total, there were 28 provenances.
5. The Icelandic provenances had significantly lower P. pini infestation than all the provenances of non‐Icelandic origin, which indicates that natural selection in Scots pine in Iceland has occurred in favour of individuals less susceptible to P. pini.

     

Double blind dose-response study of zidovudine in AIDS and advanced HIV infection. Nordic Medical Research Councils' HIV Therapy Group.

OBJECTIVE--To compare the efficacy and side effects of 400 mg, 800 mg, and 1200 mg zidovudine daily in patients with AIDS or advanced HIV infection. DESIGN--Randomised, double blind, parallel group multicentre study. SETTING--Hospital departments of infectious diseases and dermatology in Denmark, Sweden, Norway, Finland, and Iceland. SUBJECTS--474 patients: 126 (27%) with AIDS; 248 (52%) with HIV related symptoms; 100 (21%) with low CD4+ cell counts. INTERVENTIONS--Zidovudine 400 mg (160 patients), 800 mg (158), or 1200 mg (156) daily. All patients received one capsule from each of three bottles four times daily. MAIN OUTCOME MEASURES--Survival; incidence of new HIV related events; CD4+ cell count; quality of life; incidence of haematological side effects. RESULTS--460 (97%) of the 474 patients had not received zidovudine previously. The median follow up period was 19 months, during which the death rates in the three treatment groups were 23% (36/160 patients), 23% (36/158), and 19% (30/156) respectively (p = 0.49; log rank test). One year after the trial was terminated the death rates were 38% (61/160), 41% (64/158), and 44% (68/156) respectively (p = 0.54). There was no significant difference between the groups in time to a new AIDS defining event or death, average number of events per patient, decline in CD4+ cell counts, wellbeing (visual analogue scale), or Karnofsky score. Zidovudine was withdrawn in 132 (28%) patients, mainly because of side effects (71 cases; 15%). The incidences of anaemia and leucopenia, time to first dose reduction, and numbers of patients withdrawn were all dose related. CONCLUSION--Zidovudine should be limited to 400-600 mg daily in patients with AIDS or advanced HIV infection.     

A model of spatially evolving herpesvirus epidemics causing mass mortality in Australian pilchard Sardinops sagax

In 1995 mass mortality of pilchards Sardinops sagax occurred along >5000 km of Australian coast; similar events occurred in 1998/99. This mortality was closely associated with a herpesvirus. The pilchard is an important food source for larger animals and supports commercial fisheries. Both epidemics originated in South Australian waters and spread as waves with velocities of 10 to 40 km d(-1). Velocity was constant for a single wave, but varied between the epidemics and between the east- and west-bound waves in each epidemic. The pattern of mortality evolved from recurrent episodes to a single peak with distance from the origin. A 1-dimensional model of these epidemics has been developed. The host population is divided into susceptible, infected and latent, infected and infectious, and removed (recovered and dead) phases; the latent and infectious periods are of fixed duration. This model produces the mortality patterns observed locally and during the spread and evolution of the epidemic. It is consistent with evidence from pathology. The wave velocity is sensitive to diffusion coefficients, viral transmission rates and latent period. These parameters are constrained using the local and large-scale patterns of epidemic spread. The relative roles of these parameters in explaining differences between epidemics and between east- and west-bound waves within epidemics are discussed. The model predicts very high levels of infection, indicating that many surviving pilchards recovered following infection. Control appears impracticable once epidemics are initiated, but impact can be minimised by protecting juvenile stocks.     

Epidemic of mumps in a partially immune population.

The incidence of mumps in vaccinated and nonvaccinated schoolchildren was studied after a recent epidemic. Information was collected by telephone interviews with the parents and a review of the physicians'' records. The vaccine appeared to be effective, for the incidence of mumps in the 145 vaccinated children--5.5%, or 8 cases--was significantly less (P less than 0.001) than the incidence in the 350 children considered susceptible to infection--21.7%, or 76 cases. The percentage of children who had been immunized decreased with increasing age, and acquisition of immunity through natural infection had the reverse trend; thus, the proportions of children susceptible to infection in each age group were about the same, and the age-specific attack rates were similar. Although the mothers were accurate in indicating absence of vaccination, they incorrectly indicated vaccination of their children 43.0% of the time; this error in reporting could influence vaccine administration in older children. Our findings suggest that mumps vaccination may substitute for natural illness in immunizing populations, and that more extensive use of the vaccine over a broader age range is required to prevent similar epidemics in the future.     

Strain Interactions as a Mechanism for Dominant Strain Alternation and Incidence Oscillation in Infectious Diseases: Seasonal Influenza as a Case Study

Background

Many human infectious diseases are caused by pathogens that have multiple strains and show oscillation in infection incidence and alternation of dominant strains which together are referred to as epidemic cycling. Understanding the underlying mechanisms of epidemic cycling is essential for forecasting outbreaks of epidemics and therefore important for public health planning. Current theoretical effort is mainly focused on the factors that are extrinsic to the pathogens themselves (“extrinsic factors”) such as environmental variation and seasonal change in human behaviours and susceptibility. Nevertheless, co-circulation of different strains of a pathogen was usually observed and thus strains interact with one another within concurrent infection and during sequential infection. The existence of these intrinsic factors is common and may be involved in the generation of epidemic cycling of multi-strain pathogens.

Methods and Findings

To explore the mechanisms that are intrinsic to the pathogens themselves (“intrinsic factors”) for epidemic cycling, we consider a multi-strain SIRS model including cross-immunity and infectivity enhancement and use seasonal influenza as an example to parameterize the model. The Kullback-Leibler information distance was calculated to measure the match between the model outputs and the typical features of seasonal flu (an outbreak duration of 11 weeks and an annual attack rate of 15%). Results show that interactions among strains can generate seasonal influenza with these characteristic features, provided that: the infectivity of a single strain within concurrent infection is enhanced 2−7 times that within a single infection; cross-immunity as a result of past infection is 0.5–0.8 and lasts 2–9 years; while other parameters are within their widely accepted ranges (such as a 2–3 day infectious period and the basic reproductive number of 1.8–3.0). Moreover, the observed alternation of the dominant strain among epidemics emerges naturally from the best fit model. Alternative modelling that also includes seasonal forcing in transmissibility shows that both external mechanisms (i.e. seasonal forcing) and the intrinsic mechanisms (i.e., strain interactions) are equally able to generate the observed time-series in seasonal flu.

Conclusions

The intrinsic mechanism of strain interactions alone can generate the observed patterns of seasonal flu epidemics, but according to Kullback-Leibler information distance the importance of extrinsic mechanisms cannot be excluded. The intrinsic mechanism illustrated here to explain seasonal flu may also apply to other infectious diseases caused by polymorphic pathogens.     

腹泻患儿粪便A群轮状病毒抗原检测的结果分析

目的：了解本地区腹泻婴幼儿的A群轮状病毒感染情况及其流行特点。方法：采用胶体金法对我院2009年10月-2010年9月2104例有腹泻和肠炎特征的婴幼儿粪便进行A群轮状病毒抗原检测。结果：在2104例受检者中,A群轮状病毒感染的总阳性率是24．71％,其中男性感染率24．17％,女性为25．40％。不同年龄组间以1—2岁婴幼儿感染率最高,为32．13％,0-1岁为20．72％,2-5岁为12．03％。感染的季节特征是秋末冬初季（10—12月）阳性率最高,为42．82％,春末夏初季（4．6月）最低,为8．81％。结论：由A群轮状病毒感染引发的急性腹泻主要发生在1-2岁的婴幼儿,各个季节均有发生,以秋末冬初季为高发。     

Biological impact of social disruption resulting from epidemic disease

Whereas previous research on the disruptive effects of epidemic disease have focused on the ways in which epidemics affect social structure and function, this study focuses on the biological impact of social disruption. The hypothesis is that social disruption resulting from the occurrence of epidemic disease increases the biological impact of the epidemic, as assessed by disease incidence. This hypothesis is explored in terms of a "level of response" model, borrowed from Slobodkin and Rapoport (Q. Rev. Biol. 49:181-200, 1974). The Human Area Relations File (HRAF) provides ethnographic reports of social responses to epidemics. The most frequently reported response in the HRAF is flight or migration away from the locus of the epidemic, followed in frequency by extraordinary preventive and/or therapeutic measures and scapegoating. The model proposes a continuum of responses beginning with responses that are already part of the indigenous response to disease and proceeding through disruptive processes, including flight and rejection of authority systems. Social disruption increases the biological impact of epidemics by robbing the social group of important participants, dismantling public health programs, or producing general economic hardship. The model proposes a scheme for identification of situations under which particular social group responses are "biologically appropriate."     

Precancerous lesions of the cervix uteri in infertile women.

A study of 318 patients with tubal infertility and a control group of 200 unselected infertile women yielded 14 (4.4%) and 1 (0.5%), respectively, with precancerous lesions of the cervix uteri. The one patient in the control group with severe dysplasia was later shown to have tubal infertility. The overall incidence of premalignant lesions of the cervix uteri as reported to the National Cancer Registry of Norway was 0.1% for the age group and period studied. Women with tubal infertility represent a small but comparatively high risk group for the development of precancerous lesions of the cervix uteri.     

Epidemiologic analysis morbidity with meningococcal infections in the USSR]

The authors present the analysis of the incidence of epidemic cerebrospinal meningitis in the USSR from 1937 to 1974, and of meningococcus infection from 1965 to 1974. A rise of the meningococcus infection incidence from 1969 to 1974 was recorded 28 years after the elevation of 1940-1942 and was 1.5 times below this latter rise. The rise in 1969-1974 was characterized by marked signs peculiar to the infection with the droplet transmission mechanism; among those who contracted the disease prevalence was seen among children aged under 14 years (63-72%). A marked affection of juveniles was noted. Three types of the dynamic of the meningococcus infection incidence in the republics located in different climatic-geographical zones of the USSR were noted: slow, gradual increase of the level, interrupted and explosive. Such character was determined in the dynamics of the seasonal elevations of morbidity. Antiepidemic measures including a complex of nonspecific measures could not be assessed as sufficiently effective. This finds reflection in the natural course of the epidemic process of the meningococcus infection which remains uncontrolled. From the patients with generalized form of the disease meningococci of group A were isolated in 80-100% of cases, from the number of those typed. The group-specific reference of the nasopharyngeal strains depended on the epidemic situation: strains of serological group A prevailed at the period of the morbidity elevation, and other serological groups (particularly of C and B) increased at its decline.     

Regional,temporal, and seasonal variations in births and deaths: the effects of famines

A knowledge of the seasonal variation in births and deaths during normal years is important for analyses of the effects of wars, famines, epidemics or similar privations on these two variables. In studies of seasonality, multiple trigonometric regression models are more flexible than the simple sine curve. The seasonal variation in mortality in Iceland, 1856-1990, shows a strong secular decrease, and a connection between this and the epidemiological transition is considered. As a consequence of the severe famine in Finland in 1867-68, the mortality for the whole year 1868 was almost four times as high as during normal years, and the seasonality of the mortality was even more accentuated. The birth rate in Finland during 1868 was about 70 percent of that during normal years and showed an aberrant seasonality, with a strong trough from October 1868 to February 1869 (fewer conceptions between January and May 1868, when the food shortage was severe).     

Etiology of influenza according to the data of serological diagnostics in hospital patients in St. Petersburg at the period of 1968 - 2000

The specific features of the etiology of influenza in children and adults at the period of the simultaneous circulation of two subtypes of influenza virus A, according to the results in the hemagglutination-inhibition reaction in 261,490 influenza and ARD patients hospitalized in St. Petersburg in the course of 32 years, were analyzed. The results of serological diagnostics was shown to correspond to the data of the identification of influenza viruses in Russia and all over the world. At the period of epidemics diseases caused by the main infective agents of the epidemics were detected in 11.0% - 51.0% of cases and by concomitant infective agents, in 0.6% - 12.4% of cases. After the reappearance of influenza virus A(H1N1) in circulation higher frequency of mixed forms of infection and the presence of competition between the subtypes of influenza virus A was noted. In young children a decrease in differences in the proportion of influenza cases, caused by the main and concomitant infective agents, as well as between the detection of influenza in epidemic and in summer periods, was registered.     

Enteroviral aseptic meningitis in Japan, 1981-1991. A report of the National Epidemiological Surveillance of Infectious Agents in Japan.

In Japan, aseptic meningitis cases due to enterovirus infections increase every summer in various degrees with an incidence peak usually in July. During the past 11 years from 1981 through 1991, a total of 8,595 enterovirus isolations from aseptic meningitis cases were reported from 54 participating laboratories. Eight enterovirus types caused large epidemics; more than 100 isolations of each type from aseptic meningitis cases were reported for every epidemic year of the respective type. They were coxsackievirus (C) types B3 and B5, echovirus (E) types 4, 6, 7, 9, 18 and 30. Among these, the highest meningitis-associating frequency was reported for E30, representing 82.6% of the total isolations reported for the type during this period, followed by E4, 71.1%. The frequencies of E9, E7, E6 and CB5 were in a range from 54.5% to 44.4%, while that of E18 was 37.7% and that of CB3 21.0%. During the epidemics, enterovirus-associated meningitis was most frequently reported among children of 4-7 years of age. High frequencies were also shown in infants less than 1-year of age in some types. A total of 4,240 enteroviruses were isolated from cerebrospinal fluid of aseptic meningitis cases, representing 49.3% of the cases with enterovirus isolation.